PB2313: DARATUMUMAB AS A TREATMENT FOR ADULT IMMUNE THROMBOCYTOPENIA: A PHASE II STUDY WITH SAFETY RUN-IN (THE DART STUDY)
Authors: G. Tsykunova, P. A. Holme, H. Thi Thyuet Tran, T. H. A. Tvedt, L. Munthe, M. Michel, H. Frederiksen, J. Bussel, D. Kuter, W. Ghanima
Journal: HemaSphere (2022)

Background: Immune thrombocytopenic purpura (ITP) is an autoimmune condition. We hypothesize that persistent antibody-producing plasma cells can be the source of the treatment failure in some ITP patients and treatment that directly targets plasma cells may overcome resistance to treatment. Daratumumab is an anti-CD38 antibody approved for the treatment of multiple myeloma and has been successfully used to treat autoimmune hemolytic anemia and ITP in children. Aims: We initiated a multicenter, open-label total dose-escalating phase II study with a safety run-in to evaluate the safety and efficacy of daratumumab in patients with ITP (NCT04703621). The first 3 patients were included in the safety run-in between January and May 2021. We present results of a follow-up on patients treated in the safety run-in phase. Methods: Main inclusion criteria: adults (age ≥18) with primary ITP and platelet count of ≤30X109/L who experienced failure of corticosteroid therapy and at least one second-line therapy including rituximab and/or TPO- RA. A platelet count of 15-30×109/L was required for entry into the safety run-in. For the safety run-in phase, 3 patients were to receive 4 weekly subcutaneous daratumumab injections followed by a 4-week observational period. Enrollment of the next patient in this phase occurred only after the previous patient have had completed treatment and the observational period. In the subsequent phases of the study, 9 patients (Cohort 1) will receive 8 weekly injections. If no serious safety issues appear, the study will proceed to Cohort 2 in which 9 subsequent patients will receive 8 weekly daratumumab injections followed by 2 injections administered every other week. All patients will receive standard premedication before each injection with antihistamine, corticosteroid (methylprednisolone or equivalent) and paracetamol. Participants must remain on stable dose of steroids and TPO-RAs during the 2 weeks preceding the inclusion without dose escalation during the study. The primary endpoint is response defined as a platelet count ≥50×109/L in 2 measurements 12 weeks after treatment initiation for safety run-in and Cohort 1, and 16 weeks for Cohort 2, in the absence of rescue therapy after week 8. Safety will be assessed by the incidence and severity of adverse events. Secondary endpoints are duration of response, defined as duration of sustained platelet count ≥50×109/L between the end of treatment and end of study (duration does not consider the 4 weeks following the last daratumumab injection in the study); time to treatment failure defined as the time with platelet count ≥50×109/L from 4 weeks after the last daratumumab injection to the first platelet count <30×109/L. Results: As of February 01, 2022, all 3 patients have completed treatment in the safety run-in. 2/3 responded to study treatment at week 12, one relapsed by study week 24. There was only a slight decrease of immunoglobulin G levels. No serious adverse events or adverse events >grade 2 were reported in this group. Results of follow-up data on platelet response is presented in Figure 1. Enrollment in Cohort 1 is ongoing with 5 patients included so far. Image:Summary/Conclusion: Treatment with daratumumab in ITP patients shows promising results and seems safe.